Ahima R S, Dushay J, Flier S N, Prabakaran D, Flier J S
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 1997 Feb 1;99(3):391-5. doi: 10.1172/JCI119172.
The fat-derived hormone, leptin, is proposed to serve as an adipostatic signal to the brain to reduce food intake and body weight. In addition to its effects on body weight, chronic leptin treatment restores puberty and fertility to ob/ob mice with total leptin deficiency, and acute treatment substantially corrects hypogonadism in mice starved for 2 d without affecting body weight. Leptin may therefore be a critical signal, linking adiposity and reproduction. Since body weight and adiposity appear to play a critical role in the timing of puberty in humans and rodents, and leptin levels rise with increasing adiposity, we studied the effects of once daily injections of recombinant leptin on the onset of puberty in female mice weaned on day 21 and fed ad libitum. There was a linear increase in body weight during the study period, which was not altered by the dose of leptin used. Mice injected with leptin had an earlier onset of three classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared with saline-injected controls. Leptin is the first peripheral molecule demonstrated to accelerate the maturation of the reproductive axis in normal rodents. We propose that leptin is the signal that informs the brain that energy stores are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.
脂肪衍生激素瘦素被认为是一种向大脑传递的脂肪稳定信号，可减少食物摄入量和体重。除了对体重的影响外，长期使用瘦素治疗可使完全缺乏瘦素的ob/ob小鼠恢复青春期和生育能力，急性治疗可显著纠正饥饿2天小鼠的性腺功能减退，且不影响体重。因此，瘦素可能是连接肥胖与生殖的关键信号。由于体重和肥胖在人类和啮齿动物青春期启动时间方面似乎起着关键作用，且瘦素水平会随着肥胖程度的增加而升高，我们研究了每天一次注射重组瘦素对21日龄断奶并自由采食的雌性小鼠青春期启动的影响。在研究期间，体重呈线性增加，所用瘦素剂量对此没有影响。与注射生理盐水的对照组相比，注射瘦素的小鼠在三个经典青春期参数（即阴道开口、发情和周期性发情）方面启动得更早。瘦素是首个被证明能加速正常啮齿动物生殖轴成熟的外周分子。我们认为，瘦素是一种信号，它告知大脑能量储备足以支持生殖所需的高能量需求，并且可能是青春期启动时间的主要决定因素。
